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Antitumor activity and prolonged expression from a TRAIL-expressing adenoviral vector
Jeongwu Lee1, Monika Hampl, Paul Albert
1Neuro-Oncology Branch, National Cancer Institute, National Institute of Neurologic Disorders and Stroke/NIH, 10 Center Drive, Bethesda, MD, USA.
Neoplasia (New York, N.Y.)
|June 26, 2002
Summary
This study shows that an adenoviral vector expressing Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) effectively kills cancer cells and prolongs survival in mice. This suggests TRAIL gene therapy is a promising cancer treatment strategy.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells while sparing normal cells.
- Adenoviral vectors are utilized for gene delivery in therapeutic applications.
Purpose of the Study:
- To evaluate the efficacy of an adenoviral vector expressing human TRAIL cDNA (Ad.TRAIL-GFP) in cancer gene therapy.
- To assess the direct tumor cell killing and bystander effects of Ad.TRAIL-GFP.
- To determine the impact of Ad.TRAIL-GFP on survival in preclinical cancer models.
Main Methods:
- Transduction of tumor cells and normal cells with Ad.TRAIL-GFP.
- Assessment of direct and bystander tumor cell killing.
- Administration of Ad.TRAIL-GFP to mice with intracerebral glioblastomas and peritoneal carcinomatosis.
- Evaluation of transgene expression and survival rates.
Main Results:
- Ad.TRAIL-GFP demonstrated direct tumor cell killing and a significant bystander effect.
- Administration of Ad.TRAIL-GFP prolonged survival in mice with glioblastomas and breast carcinomatosis.
- TRAIL expression in normal tissue was prolonged, potentially due to reduced immune destruction of transduced cells.
Conclusions:
- Vector-mediated transduction of TRAIL shows potential as an effective cancer gene therapy strategy.
- The combination of direct killing and bystander effects contributes to therapeutic efficacy.
- TRAIL may enhance the longevity of therapeutic gene expression in normal tissues.